1.Thyroid Hormone Network Regulation in MASLD: Mechanisms and Targeted Therapies
Wen-Ping XIAO ; Yang MA ; Heng GUAN ; Sha WAN ; Wen HAN ; Bing-Bing LUO ; Wu-Feng WANG ; Fang LIU
Progress in Biochemistry and Biophysics 2026;53(3):643-661
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.
2.Research on the construction and application of a narrative nursing program based on Snyder’s hope theory for patients with advanced liver cancer
Sha NIE ; Yali SUN ; Yaxin ZHAO ; Xiaoling ZHU ; Yiyuan MA ; Jiaoqiong ZHANG
Chinese Medical Ethics 2026;39(9):1245-1253
ObjectiveTo establish a narrative nursing program for patients with advanced liver cancer based on the framework of Snyder’s hope theory, and verify its effectiveness. MethodsThe Johns Hopkins evidence-based nursing model and the Delphi method were employed to construct the narrative nursing program for patients with advanced liver cancer. Utilizing the convenience sampling method, 70 patients with advanced liver cancer hospitalized in the department of hepatobiliary surgery from May 2024 to May 2025 were selected and divided into the control group and the intervention group using the random number table method, with 35 patients in each group. The control group received routine nursing care, while the intervention group received the narrative nursing program based on Snyder’s hope theory for patients with advanced liver cancer. The Herth Hope Index, Connor-Davidson Resilience Scale (CD-RISC), Self-Rating Anxiety Scale (SAS), and Morisky Medication Adherence Scale-8 (MMAS-8) were used to compare the hope level, psychological resilience, anxiety, and medication adherence between the two groups before and after the intervention. Furthermore, nursing satisfaction was also compared. ResultsThe Delphi expert consultation results demonstrated high consistency among expert opinions, with an expert positive coefficient of 100%. Meanwhile, the authority coefficients (0.902, 0.912) and Kendall’s concordance coefficients (0.260, 0.283) were all satisfactory. Ultimately, a narrative nursing program was established, consisting of 3 primary indicators, 10 secondary indicators, and 19 tertiary indicators. Compared with the control group, the intervention group exhibited significant improvements in scores of the three dimensions regarding the hope level, the total score of psychological resilience, medication adherence, and nursing satisfaction after the intervention, and the anxiety score was markedly reduced. All differences were statistically significant (P<0.05). ConclusionThe narrative nursing program for patients with advanced liver cancer developed in this study is scientific and reliable. Its clinical application can effectively improve the psychological status and treatment behaviors of patients with advanced liver cancer, profoundly reflect the ethical care for the humanistic needs of patients, and provide an evidence-based basis for optimizing the psychological support for this population.
3.Simultaneous Determination of Ten Kinds of Neonicotinoid Residues in Water for Aquaculture by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry
Li-Sha MA ; Yi YIN ; Lin-Ting WEI ; Qi SHAN ; Xiao-Xin DAI ; Shu-Gui LIU
Chinese Journal of Analytical Chemistry 2025;53(8):1352-1361,中插96-中插99
A solid-phase extraction-ultra-performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for simultaneous determination of 10 kinds of neonicotinoid pesticide residues in aquaculture water.Based on the chemical properties of neonicotinoid pesticides and the matrix characteristics of aquaculture water,suitable temporary storage methods for water samples and appropriate solid-phase extraction columns were selected,and the extraction conditions(including elution solvents and sample loading volumes)were optimized.The method employed acetonitrile and 5 mmol/L ammonium acetate solution(containing 0.1%formic acid)as the mobile phase and an Oasis HLB solid-phase extraction column combined with PSA as a dispersive sorbent for sample purification.The method exhibited good linearity in detection of neonicotinoid in concentration range of 0.2-50 ng/mL(R2>0.99797),with a detection limit of 0.5 ng/L and a quantification limit of 1 ng/L,which were significantly lower than the maximum acceptable method detection limits(9-500 ng/L)for neonicotinoid insecticides in water published by the European Commission.In pond water,rice-fish water,and seawater,the average recoveries of the 10 target analytes were 74.6%-114.1%,with relative standard deviations ranging from 0.3%to 9.6%.Using this method,actual sample tests were conducted on the Pearl River water,Zhaoqing pond water,and Qingyuan rice-fish aquaculture water.The total concentration of five neonicotinoid pesticides in the Pearl River water ranged from 154.8 to 246.6 ng/L,the total concentration of four neonicotinoid pesticides in the Zhaoqing pond water was 95.0-176.1 ng/L,and the total concentration of three neonicotinoid pesticides in the Qingyuan rice-fish aquaculture water was 2.3-11.7 ng/L.This method was simple in operation,highly sensitive,and had strong resistance to interference.It was suitable for detection of trace neonicotinoid pesticides in aquaculture water and could provide technical support for construction of a green aquaculture environment and resolution of international trade disputes.
4.Preparation,Properties and In Vitro Release Behavior Study of Inclusion Complex of Taxifolin with 2-Hydroxypropyl-β-cyclodextrin
Shui-Xian MA ; Xin TAO ; Yun-Han YANG ; Sha XIA ; Yu-Xiang YANG ; Li YANG ; Li-Juan YANG
Chinese Journal of Analytical Chemistry 2025;53(10):1684-1693
The inclusion complex of taxifolin(TAX)with hydroxypropyl-β-cyclodextrin(HP-β-CD)was prepared by saturated aqueous solution method,and the preparation conditions such as molar ratio,volume ratio of solution,inclusion temperature and inclusion time were selected by single-factor experiment.The orthogonal design of three-level four-factor L9(34)was used to screen the preparation process of the inclusion complex,and the inclusion complex was prepared with optimal preparation process.The prepared inclusion complex was characterized by scanning electron microscopy(SEM),nuclear magnetic resonance(1H NMR,2D NMR),Fourier transform infrared spectroscopy(FT-IR),ultraviolet-visible(UV-Vis)absorption spectroscopy and X-ray powder diffraction(XRD).The inclusion ratio,biostability,solubility and in vitro release of the inclusion complex were investigated.The results of orthogonal experiments showed that the optimum conditions for preparation of the inclusion complex were as follows:the molar ratio of TAX to HP-β-CD was 1:1,the volume ratio of methanol to ultra-pure water was 1:8,the inclusion time was 8 h,and the inclusion temperature was 30℃.Under the optimal conditions,the inclusion ratio between TAX and HP-β-CD was calculated to be 1:1 by Job's curve method.According to the change of UV-vis absorption spectra,the host-guest complexation constant of 4.9488×104 L/mol was obtained by Benesi-Hildebrand curve method.The solubility of TAX increased from 1.2665 mg/mL to 19.3469 mg/mL after inclusion,demonstrating that HP-β-CD could serve as an effective host molecule for TAX,which could significantly enhance the bio-stability and solubility of the formed inclusion complex.
5.A prospective study on clinical monitoring of early cardiac myocardial dysfunction by conventional radiotherapy in N 2-N 3 non-small cell lung cancer with lymph node metastases
Yiying ZHU ; Hao ZHANG ; Weiwei OUYANG ; Shengfa SU ; Yinxiang HU ; Zhu MA ; Sha LI ; Qingsong LI ; Wengang YANG ; Xiaxia CHEN ; Haijie JIN ; Jie LIU ; Fuhuan LUO ; Zhourui LIU ; Bing LU
Chinese Journal of Radiation Oncology 2025;34(7):664-670
Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.
7.MYCN-Mediated Transcriptional Activation of IDH2 Enhances Proliferation, Migration, and Invasion in Cervical Squamous Cell Carcinoma through the HIF1-α Pathway.
Xiao Juan LIU ; Hui MA ; Xiao Yan LI ; Chun Xing MA ; Li Sha SHU ; Hui Ying ZHANG
Biomedical and Environmental Sciences 2025;38(8):1003-1008
8.Clinical value of a deep learning multi-view fusion model for diagnosing fetal conotruncal defects
Hongmei GUO ; Zhengxi DENG ; Qiuhong XU ; Sha WAN ; Jianhua LUO ; Shuangli REN ; Shuxing ZHONG ; Ting LEI ; Xiaoyan MA ; Yafui YAN
Chinese Journal of Perinatal Medicine 2025;28(10):842-849
Objective:To develop an ultrasound multi-view fusion recognition model and evaluate its clinical value in diagnosing fetal conotruncal defects (CTD).Methods:This prospective study collected cardiac ultrasound images from fetuses at 20-32 weeks of gestation undergoing prenatal ultrasound at Dongguan Maternal and Child Health Hospital between September 2022 and May 2024. The case group comprised fetuses diagnosed with CTD, while controls with normal cardiac structures were collected at a 1∶2 ratio. Both groups were divided into modeling training and validation sets at a 3∶1 ratio. One optimal standard image each from the four-chamber view, left ventricular outflow tract view, right ventricular outflow tract view, and three vessels and trachea view was included per fetus. A deep learning-based multi-view fusion recognition model was developed to differentiate normal conotruncal anatomy from CTD. Model performance was validated against post-abortion pathology or postnatal echocardiography results. SAS software was used for statistical analysis to calculate the sensitivity and specificity of three fusion models (based on positivity in any two, three, or four views, and were designated as Fusion Model 1, Fusion Model 2, and Fusion Model 3, respectively), with the optimal model determined by the maximum Youden index. Senior, intermediate, and junior prenatal sonologists independently diagnosed cases in the validation set under blinding conditions. Their diagnostic results were compared with those of the optimal model. Paired Chi-square test (Cochran's Q test) was employed to compare the differences between the diagnostic accuracy rates of sonologists at different experience levels and the sensitivity of the optimal model, thereby analyzing the auxiliary diagnostic value of the multi-view fusion recognition model. Results:The study included 88 CTD cases, excluding six cases (non-CTD diagnosed by post-abortion pathology or postnatal echocardiography or poor image quality), divided into 60 training and 22 validation cases (12 tetralogy of Fallot, four double outlet right ventricle, three transposition of great arteries, three persistent truncus arteriosus). The control group included 176 cases, excluding 15 cases (other cardiac abnormalities confirmed postnatally or poor image quality after re-evaluation), divided into 120 training and 41 validation cases. The sensitivities of Fusion Model 1, Fusion Model 2, and Fusion Mudel 3 were 0.86, 0.64, and 0.27, while their specificities were 0.76, 0.95, and 1.00, respectively. Fusion Model 1 demonstrated the highest Youden index (0.62) and was selected as optimal. Its diagnostic sensitivity showed no significant difference from senior sonologists [86% vs. 91% (20/22), Bonferroni-corrected P>0.999], but was significantly higher than intermediate [55% (12/22), Bonferroni-corrected P=0.049] and junior sonologists [32% (7/22), Bonferroni-corrected P=0.003]. Conclusion:The deep learning multi-view fusion model achieved diagnostic performance comparable to senior sonologists, demonstrating potential value in assisting CTD diagnosis, training less experienced sonologists, and supporting research and education.
9.A prospective study on clinical monitoring of early cardiac myocardial dysfunction by conventional radiotherapy in N 2-N 3 non-small cell lung cancer with lymph node metastases
Yiying ZHU ; Hao ZHANG ; Weiwei OUYANG ; Shengfa SU ; Yinxiang HU ; Zhu MA ; Sha LI ; Qingsong LI ; Wengang YANG ; Xiaxia CHEN ; Haijie JIN ; Jie LIU ; Fuhuan LUO ; Zhourui LIU ; Bing LU
Chinese Journal of Radiation Oncology 2025;34(7):664-670
Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.
10.Genotype drug resistance in human immunodeficiency virus/acquired immunodeficiency syndrome patients with antiviral therapy failure in Yunnan Province from 2021 to 2023
Hongli FAN ; Mi ZHANG ; Jiafa LIU ; Junchuan YE ; Xia LI ; Jiali WANG ; Xuemei DENG ; Lin WANG ; Sha MA ; Jianjian LI
Chinese Journal of Infectious Diseases 2025;43(7):395-402
Objective:To investigate the overall drug resistance, drug resistance trend and distribution of drug resistance mutation sites in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients with antiviral therapy failure in Yunnan Province.Methods:The demographic data and genotype drug resistance of HIV/AIDS population with antiviral therapy failure in Yunnan Province from January 2021 to December 2023 were collected and analyzed by cross-sectional investigation. Statistical analyses were performed using chi-square test.Results:Among 15 159 HIV/AIDS patients, 12 215 cases tested positive by amplification. The circulating recombinant form (CRF) 08_BC was the predominant genetic subtype, accounting for 54.97%(6 714/12 215), followed by CRF01_AE (16.14%(1 972/12 215)) and CRF07_BC (14.48% (1 769/12 215)). When the viral load was ≥200 to <1 000 copies/mL, the incidence of drug resistance was 21.48%(99/461). When it was ≥1 000 to <10 000 copies/mL, the incidence was 51.29%(2 867/5 590). When it was ≥10 000 to <100 000 copies/mL, the incidence was 69.39% (3 979/5 734). When it was ≥100 000 copies/mL, the incidence was 81.86%(352/430). A total of 7 297 drug resistant cases were detected, with a drug resistance rate of 59.74% (7 297/12 215), thus the estimated drug resistance incidence rate among the antiviral treated population in Yunnan Province was 2.00% (7 297/364 238). From 2021 to 2023, the annual drug resistance rates among patients were 60.71%(2 554/4 207), 60.28%(1 671/2 772), and 58.67% (3 072/5 236), respectively, with no statistically significant difference ( χ2=4.47, P=0.107). Among the population with antiviral therapy failure, the drug resistance rates of non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) were 93.70%(6 837/7 297), 44.10%(3 218/7 297) and 5.15%(376/7 297), respectively. The mutation sites with the highest frequencies among the three classes of drugs including NRTI, NNRTI and PI were M184V/I (46.13%(2 123/4 602)), K103N/S (37.14%(2 648/7 129)), L33F (15.50%(82/529)) and M46I/L (15.50%(82/529)), respectively. Analysis of the degree of drug resistance showed that among NNRTI drugs, nevirapine (49.01%(5 987/12 215)) and efavirenz (48.00%(5 863/12 215)) had the highest drug resistance rates, followed by emtricitabine (23.59%(2 882/12 215)) and lamivudine (23.58%(2 881/12 215)) among NRTI drugs. Conclusions:Among HIV/AIDS patients with antiviral therapy failure in Yunnan Province from 2021 to 2023, CRF08_BC is the main genetic subtype. The drug resistance rate of patients increases with the increase of HIV-1 viral load. There is no significant change in the drug resistance rate from 2021 to 2023. NNRTI has the highest drug resistance rate, followed by NRTI, and PI has the lowest. The main mutation sites are M184V/I for NRTI, K103N/S for NNRTI, and M46I/L and L33F for PI. The drug resistance rates of nevirapine, efavirenz, emtricitabine and lamivudine are relatively high.

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